This proposal will continue the existing adult ACTU at Washington University, projecting an annual accrual of 130 new patients as well as maintaining existing patients (approximately 220) on clinical trials. The ACTU will enroll 50 patients with early HIV disease in antiretroviral studies, 50 patients with advanced HIV disease in either antiretroviral studies or studies of anti-infective prophylaxis, 15 patients in protocols investigating treatment of acute opportunistic infection, 10 patients with malignancy, and 5 patients in phase 1 studies. In all, approximately 50- 60% of patients will be entered in primary infection protocols, 30-40% in studies of opportunistic infection, and 5-10% in treatment protocols for malignancy. In addition, the project will include a neurology clinical core to participate in specific neurologic protocols and to perform more detailed neurologic sub-studies of patients who are actively enrolled in other ACTG protocols. The ACTU will continue to have two clinics: the main unit at the university medical center, and the second at St. Louis Regional medical center. The latter, located at the only municipally- supported public hospital in St. Louis was specifically developed to increase access to clinical trials for minorities, drug-users and other under-represented individuals. The ACTU will direct a substantial effort communicating the goals and successes of clinical research to the community, especially health care workers. The project will maintain the existing immunology laboratory and plans to continue a virology core laboratory and a pharmacology core laboratory. The project will also maintain the pharmacology quality assurance program. Three developmental research projects are planned. A virology proposal will examine the utility of RNA PCR as a diagnostic tool for HIV, and as a marker for disease progression and response to treatment. A pharmacology proposal will develop new drug assays for antiretrovirals, correlate drug levels with response and develop the use of a hepatic cell line as a model system for understanding intracellular pharmacokinetics. A mycology proposal will establish a mycology core laboratory for the ACTG at Washington University to collect fungal isolates from patients participating in ACTG studies of systemic mycoses, type the isolates using molecular probes, examine isolates for the emergence of antifungal resistance, and develop new antifungal therapy.